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1.
Temporal localization of immunoreactive transforming growth factor beta1 in normal equine skin and in full-thickness dermal wounds 总被引：1，自引：0，他引：1
OBJECTIVE: To describe the localization of immunoreactive transforming growth factor (TGF)-beta1 in both normal skin and full-thickness dermal wounds of the limb and the thorax of the horse. STUDY DESIGN: Six full-thickness excisional wounds were created on the lateral aspect of one metacarpal region and on the midthoracic area of each horse. Sequentially collected tissue specimens from wound margins were assessed for TGF-beta1 expression by immunohistochemistry. ANIMALS: Four horses (2 to 4 years of age). METHODS: A neutralizing monoclonal anti-human TGF-beta1 antibody was used to detect the spatial expression of TGF-beta1 protein by immunohistochemical localization in biopsies obtained before wounding and at 12 and 24 hours, and 5, 10, and 14 days. RESULTS: No differences in localization of immunoreactive TGF-beta1 were detected between limb and thorax, for either intact skin or wounds. Unwounded epidermis stained moderately for TGF-beta1 protein throughout all layers, whereas the dermis was relatively devoid of immunoreactivity. During the acute stage of repair, migrating epithelium lost its stain, whereas cells of epidermal appendages remained strongly immunoreactive. The epithelium recovered its TGF-beta1 immunoreactivity during wound remodeling, although cells of the stratum corneum remained negative. Macrophages of the inflammatory exudate had positive cytoplasmic staining that diminished with time. Immunoreactivity of granulation tissue fibroblasts was evident early on and increased throughout the repair process. CONCLUSIONS: TGF-beta1 is constitutively expressed in normal, unwounded equine epithelium. Its expression is upregulated within the skin on injury and is associated with the cells involved in wound repair. CLINICAL RELEVANCE: A more precise understanding of the temporal and spatial expression of TGF-beta1 during wound repair in horses should provide the groundwork for possible future manipulations of both normal and aberrant tissue repair. 相似文献
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Vincenzo Miragliotta Jacques G. Lussier† Christine L. Theoret† 《Veterinary dermatology》2009,20(1):27-34
Healing of wounds located on the distal limbs of horses is often complicated by retarded epithelialization and the development of exuberant granulation tissue (proud flesh). Treatments that definitively resolve this pathological process are still unavailable. Molecular studies of the repair mechanism might contribute to the development of new therapeutic strategies. The study presented herein aimed to clone the full length cDNA and to study the spatio-temporal expression profile of mRNA and protein for LAMR1, previously attributed a role in wound epithelialization, during the repair of body and limb wounds in the horse. Cloning was achieved by screening a cDNA library previously derived from 7-day wound biopsies. Expression was studied in unwounded skin and in samples from 1-, 2-, 3-, 4- and 6-week-old wounds of the body and limb. Temporal gene expression was determined by real time polymerase chain reaction (RT-PCR) while protein expression was mapped immunohistochemically. Full-length cDNA for equine LAMR1 was shown to be highly similar to that of other species. The mRNA expression of LAMR1 was significantly up-regulated only in thoracic wounds, 4 and 6 weeks following wounding (upon epithelialization). Cutaneous wounding induced protein expression at both locations. Our data suggest that up-regulation of LAMR1 protein might favour epithelialization during wound healing. However, its interaction with ligands other than laminin complicates data interpretation. Future studies should quantitatively verify the temporal expression of this protein in order to provide the basis for targeted therapies that might enhance epithelialization. 相似文献
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AIM: To determine the frequency and type of skin wounds encountered by New Zealand veterinarians in their equine patients, the duration and estimated costs of treatment as well as the expected outcomes for these wounds.
METHODS: An online survey was sent to all veterinarians registered with the New Zealand Equine Veterinary Association. The survey comprised questions on the location and experience of respondents, the number of wound-related cases in relation to the total equine caseload, the type and anatomical location of wounds treated, the frequency, duration and costs of treatments, the outcome of wound treatment and an estimate of the most common causes of death or euthanasia in their equine patients.
RESULTS: The survey response rate was 110/262 (41.9%). The median number of equine cases seen by respondents was 20 (interquartile range (IQR) 6–60) per month; of these, five (IQR 2–10) were wound related. Wounds ranked third after lameness and respiratory disease for the relative frequency with which respondents encountered them. Of 102 respondents 59 (58%) reported that their clients frequently treated wounds incurred by their horse without consulting a veterinarian. Wounds on the distal limb, whether involving only the skin or also deeper structures, were reported by 86/101 (85%) respondents as the most frequently encountered. Wounds in this location also incurred the longest treatment period and were the most prone to develop complications. Finally, wounds ranked second, after colic, as the most common cause of death/euthanasia in the veterinary respondents’ equine patients.
CONCLUSIONS: The data obtained via the survey indicate that skin wounds, particularly on the distal limb, are a common occurrence in horses in New Zealand and, when they involve structures underlying the skin, are costly and time-consuming to manage and may lead to decreased performance, retirement or euthanasia. Consequently, we recommend that more effort be devoted to the education of equine veterinarians and owners, and that appropriate research funds be allocated to help improve patient outcomes. 相似文献
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OBJECTIVE--To map the expression of transforming growth factor (TGF)-beta(1), TGF-beta(3), and basic fibroblast growth factor (bFGF) in full-thickness skin wounds of the horse. To determine whether their expression differs between limbs and thorax, to understand the pathogenesis of exuberant granulation tissue. STUDY DESIGN--Six wounds were created on one lateral metacarpal area and one midthoracic area of each horse. Sequential wound biopsies allowed comparison of the temporal expression of growth factors between limb and thoracic wounds. ANIMALS--Four 2- to 4-year-old horses. METHODS--Wounds were assessed grossly and histologically at 12 and 24 hours, and 2, 5, 10, and 14 days postoperatively. ELISAs were used to measure the growth factor concentrations of homogenates of wound biopsies taken at the same timepoints. RESULTS--TGF-beta(1) peaked at 24 hours in both locations and returned to baseline in thoracic wounds by 14 days but remained elevated in limb wounds for the duration of the study. Expression kinetics of TGF-beta(3) differed from those of TGF-beta(1). TGF-beta(3) concentrations gradually increased over time, showing a trend toward an earlier and higher peak in thoracic compared with limb wounds. bFGF expression kinetics resembled those of TGF-beta(1), but no statistically significant differences existed between limb and thoracic wounds. CONCLUSIONS--Growth factor expression is up-regulated during normal equine wound repair. TGF-beta(1) and TGF-beta(3) show a reciprocal temporal regulation. Statistically significant differences exist between limb and thoracic wounds with respect to TGF-beta(1) expression. CLINICAL RELEVANCE--The persistence of TGF-beta(1) expression in leg wounds may be related to the development of exuberant granulation tissue in this location, because TGF-beta(1) is profibrotic. 相似文献
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OBJECTIVE: To determine whether transforming growth factor (TGF)-beta1 and -beta3 expression differs between equine limb wounds healing normally and those healing with experimentally induced exuberant granulation tissue (EGT). STUDY DESIGN: Six wounds were created on the lateral aspect of both metacarpi of each horse; one forelimb was untreated, and the other was bandaged to stimulate the development of EGT. Sequential wound biopsies allowed comparison of growth factor expression between the two types of wound. ANIMALS: Four horses (2 to 4 years of age; 350 to 420 kg). METHODS: Wounds were assessed grossly, histologically, and by enzyme-linked immunosorbent assay (ELISA) for TGF-beta1 and -beta3 expression at 12 and 24 hours and 2, 5, 10, and 14 days postoperatively. RESULTS: Bandaged wounds developed EGT. In all wounds, TGF-beta1 peaked early and remained elevated at 14 days. Peak TGF-beta1 concentration was higher in wounds with EGT, but not significantly so. Expression of TGF-beta3 differed from TGF-beta1, with peak TGF-beta3 concentrations being delayed. Concentrations of TGF-beta3 were higher in wounds healing normally, but this difference was not significant. CONCLUSIONS: During both normal and exuberant wound repair, the expression of TGF-beta1 occurred earlier than TGF-beta3 expression. Wounds healing with EGT tended to have higher concentrations of fibrogenic TGF-beta1 and lower concentrations of antifibrotic TGF-beta3 than wounds healing normally, although these differences were not statistically significant. CLINICAL RELEVANCE: This study suggests that the production of EGT in bandaged wounds may be related to increased expression of fibrogenic TGF-beta1 and decreased expression of antifibrotic TGF-beta3. Further investigation of the roles of TGF-beta1 and -beta3 may be important in understanding the molecular control of EGT in horses. 相似文献
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Westgate SJ Percival SL Knottenbelt DC Clegg PD Cochrane CA 《Veterinary microbiology》2011,150(1-2):152-159
Horse wounds have a high risk of becoming infected due to their environment. Infected wounds harbour diverse populations of microorganisms, however in some cases these microorganisms can be difficult to identify and fail to respond to antibiotic treatment, resulting in chronic non-healing wounds. In human wounds this has been attributed to the ability of bacteria to survive in a biofilm phenotypic state. Biofilms are known to delay wound healing, principally due to their recalcitrance towards antimicrobial therapies and components of the innate immune response. This study describes the presence of bacterial biofilms within equine wounds. Thirteen 8-mm diameter tissue samples were collected from (n=18) chronic wounds. Following histological staining, samples were observed for evidence of biofilms. Fifty one wounds and control skin sites were sampled using sterile swabs. Control skin sites were on the uninjured side of the horse at the same anatomical location as the wound. The isolated bacteria were cultured aerobically and anaerobically. The biofilm forming potential of all the isolated bacteria was determined using a standard crystal violet microtitre plate assay. Stained tissue samples provided evidence of biofilms within 61.5% (8 out of 13) equine wounds. In total 340 bacterial isolates were identified from all the equine wound and skin samples. Pseudomonas aeruginosa and Enterococcus faecium were the most predominantly isolated bacterial species from equine wound and skin samples respectively. Staphylococcus was the most commonly isolated genus in both environments. Bacteria cultured from chronic and acute wounds showed significantly (P<0.05) higher biofilm forming potential than bacteria isolated from skin. This paper highlights preliminary evidence supporting the presence of biofilms and a high microbial diversity in equine chronic wounds. The presence of biofilms in equine wounds partly explains the reluctance of many lower limb wounds to heal. Non-healing limb wounds in horses are a well documented welfare and economic concern. This knowledge can be used to shape future treatments in order to increase the healing rate and decrease the costs and suffering associate with equine wounds. 相似文献
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OBJECTIVE : To describe immunolocalization of TGF-beta receptors (RI and RII) in normal equine skin and in thoracic or limb wounds, healing normally or with exuberant granulation tissue (EGT). STUDY DESIGN : Group A: six wounds on one metacarpus and one midthoracic area. Group B: six wounds on both metacarpi, one of which was bandaged to stimulate EGT. Immunohistochemistry was used to detect RI and RII expression in wound margins. ANIMALS : Eight horses, randomly assigned to one of two study groups. METHODS : Neutralizing polyclonal anti-rabbit RI and RII antibodies were used to detect spatial expression of RI and RII in biopsies obtained before wounding, at 12 and 24 hours, and 5, 10 and 14 days after wounding. RESULTS : RI and RII were co-localized in both unwounded and wounded skin. There were no differences in cell types staining positively between tissues obtained from the limb and the thorax, or from normally healing limb wounds and limb wounds with EGT, at any time. Because of increased cellularity within EGT, staining intensity of limb wounds with 'proud flesh' was greater than limb wounds healing normally, and thoracic wounds, during the proliferative phase of repair. CONCLUSIONS : Strong expression of RI and RII, particularly in limb wounds with EGT, suggested that signalling for stimulation of matrix proteins is in place to contribute to scarring. CLINICAL RELEVANCE : This information may help determine the appropriate time for using receptor antagonists to prevent scarring of limb wounds of horses. 相似文献
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Ana Canadas Marta Santos Rui Medeiros Patrícia Dias‐Pereira 《Veterinary and comparative oncology》2019,17(4):489-496
E‐cadherin is a cell adhesion molecule that participates in several cellular processes that guarantee the maintenance of structural and functional integrity of epithelial tissues. E‐cadherin plays an important role in mammary carcinogenesis, and various studies have demonstrated the effect of CDH1 genetic variation in risk, progression and biological behaviour of human breast cancer. Although there are some recognized genetic variations in canine CDH1 gene, their influence in canine mammary tumour development and progression has not been previously evaluated. In this study, we aim to assess the influence of CDH1 SNPs rs850805755, rs852280880 and rs852639930 in the risk, clinicopathological features and clinical outcome of canine mammary tumours. A case‐control study was conducted involving 206 bitches with mammary tumours and 161 bitches free of mammary neoplasia. CDH1 SNPs rs850805755 and rs852280880 were associated with a decreased risk and a later onset of mammary tumour development. Furthermore, these SNPs were related to the development of small size carcinomas, of low histological grade and low nuclear pleomorphism. SNP rs852639930 was associated with the development of small size tumours with a non‐infiltrative, non‐invasive growth pattern. Data from the present investigation demonstrate that these CDH1 genetic variants could have a protective role in canine mammary tumours, by being associated with low risk of tumour development, delayed onset of the disease and less aggressive clinicopathological features. 相似文献
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A mare was presented for evaluation of a penetrating thoracic injury. Surgical exploration of the thoracic wound was performed, revealing diaphragmatic perforation and the presence of a foreign body lodged in the right dorsal colon. The foreign body was removed through the thoracic deficit, the colon repaired and the thoracic wound closed utilising a latissimus dorsi muscle flap. It can be concluded that successful management of thoracic wounds with concurrent abdominal viscera involvement is achievable if minimal contamination is evident. In addition reconstruction of large thoracic defects with primary muscle flaps is a viable option in the horse. 相似文献
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Gabriela S. Seiler Nigel Campbell Britton Nixon James K. Tsuruta Paul A. Dayton Samuel Jennings W. Rich Redding Meghann Lustgarten 《Veterinary radiology & ultrasound》2016,57(3):282-289
Vascular alterations play important roles in many orthopedic diseases such as osteoarthritis, tendonitis, and synovitis in both human and equine athletes. Understanding these alterations could enhance diagnosis, prognosis, and treatment. Contrast‐enhanced ultrasound (CEUS) could be a valuable method for evaluation of blood flow and perfusion of these processes in the equine distal limb, however no reports were found describing feasibility or safety of the technique. The goal of this prospective, experimental study was to describe the feasibility and safety of distal limb CEUS in a sample of six horses. For each horse, CEUS of the distal limb was performed after intravenous injections of 5 and 10 ml, as well as intra‐arterial injections of 0.5 and 1 ml contrast medium. Vital parameters were monitored and CEUS images were assessed qualitatively and quantitatively for degree of contrast enhancement. None of the horses had clinically significant changes in their vital parameters after contrast medium injection. One horse had a transient increase in respiratory rate, and several horses had mild increases of systolic blood pressure of short duration after intravenous, but not after intra‐arterial injections. Intra‐arterial injection was possible in all horses and resulted in significantly improved contrast enhancement both quantitatively (P = 0.027) and qualitatively (P = 0.019). Findings from this study indicated that CEUS is a feasible and safe diagnostic test for evaluation of the equine distal limb. Future studies are needed to assess the clinical utility of this test for horses with musculoskeletal diseases. 相似文献
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Treatment of chronic septic osteoarthritis of the antebrachiocarpal joint with a synovial‐cutaneous fistula utilising arthroscopic lavage combined with ultrasonic assisted wound therapy and vacuum assisted closure with a novel wound lavage system 
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下载免费PDF全文 This case report describes the successful management of a chronic multidrug resistant infection of the antebrachiocarpal joint with a synovial‐cutaneous fistula 7 weeks after initial trauma in a 14‐year‐old Icelandic stallion. Resolution of the multiresistant Enterobacter cloacae (extended‐spectrum β‐lactamase) infection from the joint and complete closure of the fistula was achieved by arthroscopic lavage under general anaesthesia repeated on 3 occasions, surgical debridement, ultrasound assisted wound therapy and vacuum assisted closure. Lavage of the wound with the vacuum assisted closure in place was facilitated via the novel VeraFlo instillation system consisting of specially designed therapeutic regulated accurate care pad tubing. The combination of these therapies resulted in resolution of the septic arthritis and fistula. Six weeks after admission the horse was discharged from the hospital with a completely healed wound and was not lame at a walk. 相似文献
16.
OBJECTIVE: To evaluate the effect of intramuscular administration of recombinant equine growth hormone on healing of full thickness skin wounds on equine limbs. STUDY DESIGN: Experimental. ANIMALS: Nine Standardbred horses. METHODS: In study 1, standardized full thickness skin wounds (2.5 x 2.5 cm) were made over the dorsomedial aspect of the mid-cannon bone of 1 forelimb and 1 hindlimb in 9 horses. Wounds were bandaged without treatment (control subjects) and videorecorded twice weekly until healed. Then, in study 2, similar wounds were created on the opposite limbs; 6 horses were administered intramuscular recombinant equine growth hormone (10 microg/kg daily for 7 days, then 20 microg/kg daily for 49 days), and 3 horses (control subjects) were administered equivalent volumes of sterile water. Wounds were videorecorded twice weekly until healed. Wound healing variables were measured from the videorecordings using a computer software package and analyzed as a randomized complete block design factorial analysis of variance; significance was set at P <.05. RESULTS: No differences in the measured variables were detected between wounds in study 1 and the control wounds in study 2. In recombinant equine growth hormone-treated horses, wounds retracted more during treatment and contracted faster after treatment stopped when compared with wounds from untreated horses. No other treatment effects were detected. CONCLUSIONS: Recombinant equine growth hormone seemingly increases wound retraction. After treatment ceases, wound contraction increases. CLINICAL RELEVANCE: Intramuscular administration of recombinant equine growth hormone (10 microg/kg daily for 7 days, then 20 microg/kg daily for 49 days) does not appear to have any beneficial clinical effect on healing of equine limb wounds. 相似文献
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Valrie Dubuc lodie Lepault Christine L. Theoret 《Canadian journal of veterinary research》2006,70(3):206-210
Wound repair in horse limbs is often complicated by excessive fibroplasia and scarring. Occlusion of the microvessels populating the granulation tissue appears to be involved in the excessive accumulation of extracellular matrix during the repair of limb wounds. This study aimed to determine whether endothelial cell hypertrophy or hyperplasia, or both, contribute to microvascular occlusion and whether the pericyte is involved in this anomaly. We created 5 wounds, each 2.5 x 2.5 cm, on both forelimbs and on the body of 6 horses. One limb was bandaged to stimulate excessive wound fibroplasia. Weekly biopsy specimens were evaluated by transmission electron microscopy to measure microvessel luminal diameters and the surface area of endothelial cells and to count endothelial cells and pericytes. Microvessels were occluded significantly more often in limb wounds than in body wounds. The surface area of endothelial cells lining occluded microvessels (mean +/- standard error, 28.4013 +/- 1.5154 microm2) was significantly greater (P = 0.05) than that of cells lining patent microvessels (26.2220 +/- 1.5268 microm2). Conversely, neither the number of endothelial cells nor the number of pericytes differed between patent and occluded microvessels or between limb and body wounds. Furthermore, the wound location and the status of the microvessels (patent or occluded) did not alter the ratio of endothelial cells to pericytes. These data suggest that endothelial cell hypertrophy might play a role in the microvascular occlusion present in granulation tissue of limb wounds in horses, but the contribution of the pericyte remains obscure. 相似文献
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S. M. M. Nakayama Y. Ikenaka A. Hayami H. Mizukawa W. S. Darwish K. P. Watanabe Y. K. Kawai M. Ishizuka 《Journal of veterinary pharmacology and therapeutics》2016,39(5):478-487
Research on drug metabolism and pharmacokinetics in large animal species including the horse is scarce because of the challenges in conducting in vivo studies. The metabolic reactions catalyzed by cytochrome P450s (CYPs) are central to drug pharmacokinetics. This study elucidated the characteristics of equine CYPs using diazepam (DZP) as a model compound as this drug is widely used as an anesthetic and sedative in horses, and is principally metabolized by CYPs. Diazepam metabolic activities were measured in vitro using horse and rat liver microsomes to clarify the species differences in enzyme kinetic parameters of each metabolite (temazepam [TMZ], nordiazepam [NDZ], p‐hydroxydiazepam [p‐OH‐DZP], and oxazepam [OXZ]). In both species microsomes, TMZ was the major metabolite, but the formation rate of p‐OH‐DZP was significantly less in the horse. Inhibition assays with a CYP‐specific inhibitors and antibody suggested that CYP3A was the main enzyme responsible for DZP metabolism in horse. Four recombinant equine CYP3A isoforms expressed in Cos‐7 cells showed that CYP3A96, CYP3A94, and CYP3A89 were important for TMZ formation, whereas CYP3A97 exhibited more limited activity. Phylogenetic analysis suggested diversification of CYP3As in each mammalian order. Further study is needed to elucidate functional characteristics of each equine CYP3A isoform for effective use of diazepam in horses. 相似文献
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OBJECTIVE: To investigate the effects on wound healing of transforming growth factor-beta 1 as a topical treatment to full-thickness, excisional wounds of the distal limb of horses. DESIGN: A randomised block study using four horses, each with wounds assigned to four treatment groups. ANIMALS: Four adult Standardbred geldings. PROCEDURE: Four, 4 cm2, full-thickness wounds were created on the dorsomedial and dorsolateral aspect of the metacarpus or metatarsus of each limb of four horses, giving a total of 64 wounds. For each limb, wounds were randomly assigned to four treatment groups: no treatment (control), carrier (Methyl Cellulose gel), 50 ng/wound rhTGF-beta 1 in carrier, and 500 ng/wound rhTGF-beta 1 in carrier. Wounds were treated on day 0 and day 8. Effects of treatment were evaluated on the basis of the presence of exuberant granulation tissue requiring excision, number of times excision was required, total wound area, area of epithelialisation, area of granulation, and histological evaluation of biopsy samples of wounds on day 8 and excised wounds on day 21. RESULTS: Topical application of TGF-beta 1 at the two concentrations studied had no significant effect on the total area of wounds (P = 0.7), the area of granulation tissue (P = 0.78), the area of epithelialisation (P = 0.92), histological assessment or subjective clinical assessment of wounds. CONCLUSION: TGF-beta 1 had no beneficial effects on wound healing. Additional trials are needed to test if it has value for wound treatment in horses. 相似文献
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OBJECTIVE: To evaluate the effect of a commercially available 25% propylene glycol hydrogel preparation (Solugel; Johnson and Johnson Medical, North Ryde, Australia) on healing of full-thickness skin wounds on the distal aspect of the limb in horses. STUDY DESIGN: Experimental. ANIMALS: Eight Standardbred horses. METHODS: Standardized (2.5 x 2.5 cm) full-thickness skin wounds were created over the mid-dorsomedial aspect of both metacarpi in 8 horses. One wound in each horse was dressed with saline solution (0.9% NaCl) soaked gauze, and one was treated with Solugel under dry regular gauze; wounds were then bandaged with gauze-coated cotton wool and elastic adhesive bandages. Wounds were videorecorded and rebandaged twice weekly until healed. Wound healing variables were measured from the videorecordings using a computer software package and analyzed as a randomized complete block design with repeated measures. Where necessary variables were made positive for analysis; significance was set at P <.05. RESULTS: The area of the wound at the first bandage change did not vary between treated and untreated wounds. Treatment had no effect on the total rate of healing, rate of healing during the retraction phase of healing, rate of healing after the retraction phase was complete, or the amount the wounds retracted. CONCLUSIONS: Using this model of wound healing, Solugel had no effect on second intention healing of distal limb wounds in horses. CLINICAL RELEVANCE: Solugel does not appear to have any beneficial effect on healing of small full-thickness skin wounds to the distal limb of horses. 相似文献